The digestive processes in humans and in monogastric animals such as pigs, birds and horses, involves acid digestion in the stomach followed by absorption of simple sugars, amino acids, fats etc from the small intestine. The undigested material then passes into the large intestine which contains a dense population of bacteria and where fermentation of fibrous material and undigested sugars, starches and carbohydrates occurs. Ruminants such as sheep and cattle, related animals and some kangaroo species have a forestomach in which feed is fermented prior to acid digestion. These animals also have a hind gut where fermentative digestion also occurs.
The hind gut (or large intestine) varies in size and structure depending on the nature of the diet and the extent of fibre digestion which normally occurs. In humans and animals it consists of a colon and caecum and both of these compartments can vary in their size and in their complexity of structure. Normal fermentation results in the production of volatile fatty acids (VFA) which are absorbed from the gut. In the hind gut the pH is maintained, under normal conditions within the range 6 to 7.5, as it is within this range that bacterial fermentation is most efficient. If starch, sugar or other carbohydrate enters the hind gut it is rapidly fermented, and this rapid fermentation can lead to the accumulation of lactic acid, which is a stronger acid than the VFA and it is not absorbed as quickly. The accumulation of lactic acid leads to a decline in pH. These acidic conditions can result in damage to and death of bacteria with the release of endotoxins. The low pH can also initiate the release of various peptide hormones and/or enzymes by the gut wall and these molecules can be active in different parts of the body. The endotoxins and/or hormones and/or other chances which result from high levels of hind gut fermentative activity may affect numerous functions of the body. There is therefore a wide range of biological consequences which result from an acidic pattern of fermentation in the hind gut.
Consequently, there are several adverse effects which excessive levels of starch and/or sugar can have on humans and animals. These include behavioural changes in horses and humans, diarrhoea in animals and humans, skin disorders in humans and infections of the hind gut associated with acidic conditions. It is also known that severe carbohydrate overload in animals can cause significantly reduced intake and in some instances, death. Under extreme models of carbohydrate overload in which non-physiological amounts of glucose and/or starch are administered to animals, acidic patterns of fermentation develop, leading to conditions such as diarrhoea in ruminants. Under normal nutritional circumstances isolated episodes of diarrhoea are not considered to be a result of incomplete carbohydrate absorption in the small intestine and the occurrence of excessive fermentation in the hind gut. It has generally been considered to be a fact in human and animal digestive physiology, that starches and sugars are completely digested and absorbed from the digestive tract prior to the hind gut. Because complete digestion and absorption has been assumed, the occurrence of hind gut fermentative acidosis has never been considered as a potential health problem under normal dietary conditions. Therefore, it has never been recognised as the possible primary cause of abnormalities such as behavioural changes, diarrhoea and skin disorders linked to the inclusion of starches and sugars in the diet. Consequently the treatment of the conditions such as behavioural changes, the control of diarrhoea, prevention of skin diseases and infections of the hind gut associated with acidic conditions, through treatments to control acid accumulation in the hind gut, are not known in any species under normal conditions.
The link between the inclusion of carbohydrate such as starch and sugars in the diet of horses and humans and subsequent adverse behaviour is known. The mechanism by which the carbohydrate source in the diet effects behaviour has not been understood and in the past treatment has relied totally on avoidance. Horses fed high levels of grain become excitable, difficult to handle and they develop a range of behavioural characteristics such as coprophagy, wood chewing and grasping or wind sucking. These behavioural abnormalities are currently overcome or reversed by reducing the amount of cereal grain in the diet or completely removing the source of starch or carbohydrate. This is the normal practice when the behavioural problems become severe. There has hitherto been no other known way of treating this condition. Similarly, in humans, a proportion of children are known to become hyperactive when they consume certain foods rich in sugars and/or processed starch. The consumption of these feeds is also thought to be associated with the condition "attention deficit disorder". Hitherto, the only known treatment for these behavioural changes has been avoidance of processed starches and sugars. In intensively housed pigs fed diets containing high levels of cereal grain, the problem of tail biting and other patterns of "bored" behaviour have been recognised and treated by providing a range of alternative activities for the pigs, such as balls, ropes and chains for them to push and play with.
There are numerous causes of diarrhoea. Diarrhoea is a result of excessive secretion of fluids into the gut and/or a failure to absorb sufficient fluid from the gastro-intestinal tract. Fluid loss into the gut can occur through changes in gut permeability, through increased osmotic concentration in the gut or through abnormal intestinal motility. The permeability can be affected by any factors which produce inflammation and increased capillary permeability. It can also be increased by raised venous pressure or any factor which disrupts the tight packing of the epithelial cells in the hind gut. Osmotic diarrhoea can result from the inclusion of non-absorbable solutes in the diet or through the production of osmotically active molecules within the gut. The osmotic pressure can be increased either by microbial breakdown of large particles to smaller particles and through the enzymatic conversion of large molecules such as starch to a greater number of small molecules such as volatile fatty acids and lactic acid. The process of rapid fermentation of starches and sugars can lead to a sudden increase in osmotically active molecules and diarrhoea.
Intestinal motility may increase the incidence of diarrhoea through increased rate of gastric emptying, increased small bowel transit and increased rate of passage through the hind gut. These processes result in more secretion into the gut and reduced absorption of solutes and this leads to diarrhoea. The specific causes of abnormal gut motility are largely unknown. Conditions such as irritable colon syndrome or irritable bowel disease are thought to be associated with abnormal gut motility. There is no known treatment for these conditions.
The mechanism by which viral agents cause diarrhoea is not known. Infection with transmissible gastro-enteritis virus, or human rotavirus are known to reduce the absorptive efficiency of the gastro-intestinal tract. There does not appear to be evidence that they increase secretion into the gut. There is no known treatment against viral diarrhoea.
Fluid loss into the gut by active mechanisms occurs in response to a variety of bacterial exotoxins. These exotoxin or enterotoxins are thought to promote active secretion of electrolytes and water through activation of the enzyme adenyl cyclase. Examples of bacteria known to promote diarrhoea include Vibrio cholerae, enterotoxicogenic Escherichia coil, Shigella dysenteriae, Bacillus cereus, Clostridium perfringens, Salmonella enteriditis and Klebsiella pneumoniae. Diarrhoea of toxic microbial origin is thought to be the most common type of diarrhoea. This form of diarrhoea is commonly created by vaccination in the case of cholera and/or through antibiotic treatment for these and other microbial pathogens. It is therefore well known to treat diarrhoea with antibiotic agents specifically effective against pathogenic bacteria in the gut. Broad spectrum antibiotics such as co-trimoxazol, erythromycin, penicillins, cephalosporins etc are used in these situations at therapeutic concentrations to clear the gut of pathogenic organisms. This type of diarrhoea caused by active fluid loss through the effect of pathogenic bacteria via the enzyme adenyl cyclase is completely different to the osmotic diarrhoea caused by accumulation of osmotically active particles and molecules in the intestine. While diarrhoea associated with the active secretion resulting from toxic bacteria has been commonly treated using antibiotics there has hitherto been no treatment available for osmotic diarrhoea other than avoidance of feeds and substrates known to cause the problem. It is this form of diarrhoea that is the object of the invention.
The blue green algae Microcystis aeruginosa is widely distributed in water sources and is also known to produce a toxin responsible for initiating diarrhoea. The only known treatment for this is avoidance of polluted water.
Diarrhoea can also be caused by abnormal endocrine function which produces abnormally high levels of secretion or which inhibits normal intestinal absorption. These hormonal abnormalities are poorly understood and there are no known methods of treating these abnormalities.
There are numerous recorded examples of skin conditions such as psoriasis which respond to changes in the amount and type of carbohydrate consumed. There are also many well documented cases where the practice of food combining has reduced the incidence of skin disorders such as psoriasis. The practice of food combining is designed to maximise the efficiency with which starches and sugars are absorbed from the small intestine. While the link between certain types of starch in the diet and skin disorders is well known the mechanism by which starches and sugar in the diet affect these skin abnormalities is not understood. Hitherto, the only existing treatment for these skin conditions is therefore avoidance of foods known to cause the problem and the use of topical application of steroidal creams to control the symptoms.
The hind gut disease, swine dysentry, is caused by pathogenic bacteria Serpulina (previously Treponema) hysdysenteriae. It has been shown that infection with S. hyodysenteriae can be prevented by feeding boiled rice instead of wheat-based diets. Hitherto, the control of this disease through preventing acidic conditions in the hind gut is not known. Acidity in the hind gut predisposes it to infection by bacteria and other pathogens which tolerate acidic conditions. The control of these pathogens by maintaining normal pH in the hind gut is not known.
Accordingly there is a need for improved treatment or prophylaxis of conditions resulting from the accumulation of acid in the gastrointestinal tract of a human or an animal, said accumulation resulting from fermentation of carbohydrate in the gastrointestinal tract of the human or animal.